My research objective is to determine the role of lymphocyte DNA synthesis in propagating the immune response and lymphoid malignancies. DNA synthesis in vitro in lymphocytes stimulated by antigens or by phytohemagglutinin is followed by DNA excretion into the culture medium. The base-pair complexity of excreted DNA, measured by Cot analysis, is 1/20 that of the total lymphocyte genome; thus excreted DNA cannot simply result from cell lysis. It is not known whether excreted DNA results from initiation of DNA synthesis in cells which are unable to complete mitosis and which then excrete initiation sequences, or whether excreted DNA is an unusual functional step in the lymphocyte's contribution to the immune response. If DNA excretion is a means of information transfer between cells it could be of importance in the propagation of lymphoid malignancies. Lymphocytes will be cultured under conditions permitting log growth. Reassociation of purified excreted DNA will be driven by DNA from normal tissue and from lymphoid malignancies to define the number of copies present in these tissues. The mechanism of DNA excretion through the plasma membrane will be studied. Excreted DNA will be hybridized to different types of RNA, and DNA excreted from cultures stimulated by different antigens will be cross hybridized in an attempt to associate a cell function with excreted DNA.